- 11-β-hydroxysterols as possible endogenous stimulators of mitochondrial biogenesis as inferred from epicatechin molecular mimicry
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Currently, there is great interest in identifying endogenous (i.e. physiological) stimulators of mitochondrial biogenesis (MB), in particular, those that may mediate the effects of exercise. The molecular size of the cacao flavanols (epicatechin and catechin) highly resembles that of sterols and epicatechin has been reported to activate cells surface receptors leading to the stimulation of MB in endothelial and skeletal muscle cells translating into enhanced exercise capacity. We therefore hypothesize, that epicatechin may be acting as a structural mimic of an as yet unknown sterol capable of stimulating MB. We developed a new synthetic process for obtaining enantiomerically pure preparations of (-)-epicatechin and (+)-epicatechin. Applying spatial analytics and molecular modeling, we found that the two isoforms of epicatechin, (-) and (+), have a structural resemblance to 11-β-hydroxypregnenolone, a sterol with no previously described biological activity. As reported in this proof-of-concept study performed in primary cultures of endothelial and muscle cells, 11-β-hydroxypregnenolone is one of the most potent inducers of MB as significant activity can be detected at femtomolar levels. The relative potency of (-)/(+)-epicatechin isoforms and on inducing MB correlates with their degree of spatial homology towards the 11-β-hydroxypregnenolone. On the basis of these results, the detailed in vivo characterization of the potential for these sterols to act as endogenous modulators of MB is warranted.
- Dugar, Sundeep,Villarreal, Francisco,Hollinger, Frank H.,Mahajan, Dinesh,Ramirez-Sanchez, Israel,Moreno-Ulloa, Aldo,Ceballos, Guillermo,Schreiner, George
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- New steroid 11-ketone group oxidation synthesizing process
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The invention discloses a new steroid 11-ketone group oxidation synthesizing process. The method comprises that in a nonprotic organic solvent, under conditions of dimethyl sulfoxide (DMSO) as an oxidant, an organic alkali, dichlorophenyl phosphate and a piperidine aminoxyl free radical, a steroid 11-alpha hydroxyl compound is subjected to an oxidation reaction to generate a steroid 11-ketone group compound, the reaction temperature is -10 DEG C to a solvent reflux temperature, and the piperidine aminoxyl free radical is selected from the group consisting of a 2,2,6,6-tetramethylpiperidine-1-oxyl free radical or an analogue thereof.
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Paragraph 0130; 0131; 0132
(2016/10/09)
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- HYDROXYSTEROID COMPOUNDS, THEIR INTERMEDIATES, PROCESS OF PREPARATION, COMPOSITION AND USES THEREOF
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The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds.
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Page/Page column 47; 61; 62
(2016/02/09)
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- Raw synthesis and mitochondrial function postischemic mitochondria diseases related to the lack or for use in new compd. 11β-hydroxysteroid
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The present invention provides novel compounds of 112-hydroxy steroids and compositions and their application as pharmaceuticals for preventing or reversing injury to mitochondria, for treating or preventing diseases relating to mitochondrial dysfunction or depletion, and for inducing regeneration or restructuring of mitochondria as a means of treating diseases relating to abnormalities in mitochondrial structure and function in a human or animal subject. Also disclosed herein are methods for diagnosing injury to mitochondria and for diagnosing the success or failure of therapeutics designed to treat, prevent, or reverse injury to or depletion of mitochondria.
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Paragraph 0225
(2016/10/08)
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- Efficient C-21 Deoxygenation of 21-Alkoxy-20-keto Corticoid Steroids with Trimethylsilyl Iodide in the Presence of Methanol
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Reaction of 21-alkyl ethers 1, 4-6, 8, and 9 with a large excess of trimethylsilyl iodide (TMSI) produced the deoxygenated products 3 and 11 in low to moderate yields along with a small amount of 21-alcohols 2 and 10.The deoxygenation reaction in the presence of 1.5 molar equiv of MeOH gave the products in much higher yields than those without MeOH, except the reaction of the ethyl and n-propyl ethers 4 and 5.Treatment of 1 and 8 with trimethylsilyl chloride/NaI in the presence of MeOH gave similar results to those with TMSI.Compound 3 was also produced in high yields by reaction of 1 and 4 with HI under mild conditions.On the other hand, treatment of 17α-ketol 7 with TMSI in the presence of MeOH yielded 17aβ-methyl D-homo steroid 15.The results along with deuterium-labeling experiments with MeOD and IR and 1H NMR spectral analysis during the reaction with TMSI suggest that dealkylation of the 21-alkyl ethers precedes the deoxygenation, in which HI produced in situ by reaction of MeOH with TMSI would be involved.
- Nagaoka, Masao,Kunitama, Yurie,Numazawa, Mitsuteru
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p. 334 - 338
(2007/10/02)
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- 18-Substituted Steroids. Part 8. An Improved Synthesis of 11β,18,21-Trihydroxypregn-4-ene-3,20-dione ('18-Hydroxycorticosterone')
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'18-Hydroxycorticosterone' (1) has been prepared from 11β-formyloxy-20-hydroxypregn-4-en-3-one (6) by application of the 'hypoiodite' series of reactions , followed by acetoxylation at C-21 by lead tetra-acetate in acetic acid.Alkaline hydrolysis then gave 18-hydroxycorticosterone.
- Kirk, David N.,Slade, Christopher J.
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p. 703 - 705
(2007/10/02)
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